Structure-Based Virtual Screening: Identification of Novel Quorum-Sensing Inhibitors to Interfere with the Formation of <i>Pseudomonas aeruginosa</i> Biofilm

Abstract

Background: Drug-resistant Pseudomonas aeruginosa (P. aeruginosa) is among the most important opportunistic human pathogens that may infect military personnel during war by generating a broad range of virulence factors, the expression rates of which are firmly arranged by cell density-dependent cell-to-cell signaling called quorum sensing (QS). Objectives: This study aimed at identifying putative inhibitors of LasR by structure-based virtual screening on ZINC database, testing prospective candidates on pqsE with computer aided inhibition studies followed by structure analysis, and examining the extension of specific drugs with potential anti-virulence properties for the treatment of infections induced by drug-resistant P. aeruginosa. Methods: Structure-based virtual screening in ZINC database was used through Autodock Vina in order to assess putative inhibitors of LasR. Prospective candidates’ inhibitory efficiency on pqsE was examined by means of computer aided inhibition studies followed by structure analysis. Results: Twenty possible quorum sensing inhibitors were introduced that could be used in different conditions to inhibit quorum sensing and thus reduce bacterial resistance and pathogenicity. A software was also designed to provide graphical user interface to vina and to automate the process of virtual screening. Conclusions: This study provided a perspective for development of specific drugs with potential anti virulence properties in military medicine for the treatment of infections induced by drug-resistant P. aeruginosa